The objectives of the proposed studies are to obtain information concerning 1) the genetic control and evolutionary diversification of immunoglobulin-constant regions through direct primary structure analysis of immunoglobulins from phylogenetically primitive Elasmobranch species; 2) the structural nature of a serum and cell-surface macromolecule found in these species which is antigenically related to mammalian beta 2-microblobulin (beta 2m), and 3) the possible association of the beta 2m-like molecule with other polypeptides on the surfaces of shark leukocytes. Immunoglobulin will be isolated from the sera of sharks. CNBr and tryptic digests will be made of the immunoglobulin heavy chains and the resulting fragments will be subjected to N-terminal amino acid sequencing. Identification of interchain and intrachain disulfides will be facilitated by selective reduction and radioalkylation. Prototype sequences will be constructed, compared to sequences of mammalian immunoglobulin and the role of various genetic mechanisms in the evolution of constant regions postulated. Isolation of the shark serum protein resembling beta 2m (which in mammalian species exhibits substantial homology with immunoglobulin-constant regions) will be carried out in parallel. N-terminal sequences analysis and characterization of cysteine-containing peptides will be used to examine the homology of the molecule with constant regions of shark immunoglobulin and mammalian beta 2m. Antisera raised to the shark equivalent of beta 2m will be used to explore the distribution of beta 2m-like proteins in other lower vertebrate and invertebrate species using radioimmunoassay techniques and to examine possible associations of beta 2m-like proteins with other membrane polypeptides on the surfaces of shark leukocytes. The possible relationship of these polypeptides to the membrane components known to be products of the major histocompatibility complex in higher vertebrates will be examined.